Cellular senescence promotes meibomian gland dysfunction in a chronic graft-versus-host disease mouse model

Shinri Sato, Yoko Ogawa, Eisuke Shimizu, Kazuki Asai, Takahiro Okazaki, Robert Rusch, Masatoshi Hirayama, Shigeto Shimmura, Kazuno Negishi, Kazuo Tsubota

研究成果: ジャーナルへの寄稿学術論文査読

抄録

Purpose: Aging is a well-established risk factor for meibomian gland dysfunction (MGD). We previously reported an accelerated cellular senescence phenomenon in the lacrimal glands of a murine model of chronic graft-versus-host disease (cGVHD). Herein, we aimed to elucidate the relationship between cellular senescence and MGD in cGVHD mice, utilizing the senolytic agent ABT-263. Methods: A cGVHD mouse model was established through allogeneic bone marrow transplantation (BMT) from B10.D2 to BALB/c mice. Subsequently, cGVHD mice were treated with either ABT-263 or vehicle. The eyelids of recipients were analyzed at 4-week intervals post-BMT in both groups. Results: Meibomian gland (MG) area was significantly smaller in cGVHD mice than in syngeneic control mice. ABT-263-treated mice retained a significantly larger MG area than their vehicle-treated counterparts. Pathological and immunohistochemical examinations revealed significant reductions in eyelid tissue inflammation and pathological fibrosis in the ABT-263 group compared to that in the vehicle-treated group. Additionally, expression of DNA damage markers, senescent cell markers, and senescence-associated secretory phenotype (SASP) factors was elevated in the eyelids of cGVHD mice compared with that in syngeneic mice. The expression of these cellular senescence-associated molecules was considerably suppressed in ABT-263-treated eyelids compared to that in vehicle-treated ones. Conclusions: Cellular senescence, along with expression of SASP factors, exhibited increased activity in the eyelids, particularly in the MGs of cGVHD mice. ABT-263 mitigated the severity of MGD. These findings highlight the potential of targeting cellular senescence as an effective approach for MGD treatment in cGVHD.

本文言語英語
ページ(範囲)198-210
ページ数13
ジャーナルOcular Surface
32
DOI
出版ステータス出版済み - 04-2024

All Science Journal Classification (ASJC) codes

  • 眼科学

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